NEUROCHEMICAL ACTIONS OF PSYCHOTROPIC DRUGS

这项应用的长期目标是阐明神经化学 大脑中的信号转导系统的各个方面， 精神药物的行动。 建议进行研究，以澄清 磷脂酰肌醇和一氧化氮信使系统的性质。 肌醇-1，4，5-三磷酸（IP 3）受体蛋白的性质将 被描述。 磷酸化的生物化学和功能作用 并检测受体的糖基化。 职能作用 受体的磷酸化和糖基化将通过 脂质体中的IP 3受体蛋白的重构系统， IP 3选择性地刺激钙流IP 3受体的性质 将外周组织中的蛋白质与中枢受体进行比较。 肌醇（1，3，4，5）四磷酸（IP 4）的受体蛋白将是 提纯 将开发针对IP 4受体蛋白的抗血清， 其免疫组织化学定位。 利用纯化的IP 4受体 蛋白质重组到脂质体中，将努力鉴定 潜在的功能，如离子通量的调解。 Calmedin，一种膜 大脑中的相关蛋白，介导钙的能力， 抑制IP 3受体结合，将其纯化 纯化的钙调蛋白和IP 3受体蛋白将在激酶中进行检测， 产生IP 4的细胞会被净化 纯化酶的抗血清 蛋白质将用于免疫组织化学。 一氧化氮（NO）是神经元内可能的信使， 大脑中的相互作用。 转换之间的关系 精氨酸转化为瓜氨酸和NO的形成将在 各种系统。 所用内源性精氨酸库的性质 通过检测3 H-精氨酸的摄取， 和内源性精氨酸水平的改变。 代理人的影响 影响自由基形成的因素将在NO和环GMP上进行检查 阵 NO合成的细胞来源将利用 神经系统突变小鼠 NO形成酶将被纯化， 免疫组织化学定位用抗血清。

The long-term goal of this application is to elucidate neurochemical aspects of signal transduction systems in the brain which may be the site of action for psychotropic drug actions. Studies are proposed to clarify properties of the phosphoinositide and nitric oxide messenger systems. Properties of the inositol-1,4,5-triphosphate (IP3) receptor protein will be characterized. The biochemical and functional role of phosphorylation and glycosylation of the receptor will be examined. Functional role of phosphorylation and glycosylation of the receptor will be evaluated through a reconstituted system of the IP3 receptor protein in liposomes whereby calcium flux is stimulated selectively by IP3 Properties of IP3 receptor protein in peripheral tissues will be compared with the central receptor. The receptor protein for inositol (1,3,4,5) tetrakisphosphate (IP4) will be purified. Antisera will be developed to the IP4 receptor protein to permit its immunohistochemical localization. Utilizing the purified IP4 receptor protein reconstituted into liposomes, efforts will be made to identify potential functions ,such as mediation of ion flux. Calmedin, a membrane associated protein in the brain which mediates the ability of calcium to inhibit IP3 receptor binding, will be purified Interactions between purified calmedin and IP3 receptor protein will be examined in kinase, which generates IP4, will be purified. Antisera to the purified enzyme proteins will be employed for immunohistochemistry. Nitric oxide (NO) will be characterized as a possible messenger in neuronal interactions in the brain. The relationship between the conversion of arginine to citrulline and the formation of NO will be examined in a variety of systems. The nature of the endogenous arginine pool employed for NO biosynthesis will be explore by examining the uptake of 3H-arginine and alterations in endogenous arginine levels. The influence of agents that affect free radical formation will be examined on NO and cyclic GMP formation. The cellular source of NO synthesis will be explored utilizing neurologic mutant mice. The NO forming enzyme will be purified and antisera raised for immunohistochemical localization.